A slow-cycling subpopulation of melanoma cells with highly invasive properties.

Abstract

Melanoma is a heterogeneous tumor with different subpopulations showing different proliferation rates. Slow-cycling cells were previously identified in melanoma, but not fully biologically characterized. Using the label-retention method, we identified a subpopulation of slow-cycling cells, defined as label-retaining cells (LRC), with strong invasive properties. We demonstrate through live imaging that LRC are leaving the primary tumor mass at a very early stage and disseminate to peripheral organs. Through global proteome analyses, we identified the secreted protein SerpinE2/protease nexin-1 as causative for the highly invasive potential of LRC in melanomas.

• Authors: M Perego, M Maurer, J X Wang, S Shaffer, A C Müller, K Parapatics, L Li, D Hristova, S Shin, F Keeney, S Liu, X Xu, A Raj, J K Jensen, K L Bennett, S N Wagner, R Somasundaram, M Herlyn
• Journal: Oncogene (Oncogene) Vol. 37 Issue 3 Pg. 302-312 (01 18 2018) ISSN: 1476-5594 [Electronic] England
• PMID: 28925403 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• SERPINE2 protein, human
• Serpin E2

Topics

• Animals
• Cell Cycle
• Cell Line, Tumor
• Cell Separation (methods)
• Flow Cytometry (methods)
• Humans
• Melanocytes (metabolism, pathology)
• Melanoma (pathology)
• Mice
• Neoplasm Invasiveness (pathology)
• Proteomics
• Serpin E2 (metabolism)
• Skin (cytology, pathology)
• Skin Neoplasms (pathology)
• Xenograft Model Antitumor Assays